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Pharmacol Biochem Behav. 2002 Apr;71(4):795-805.

Nicotinic--serotonergic interactions in brain and behaviour.

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Psychopharmacology Research Unit, Centre for Neuroscience, GKT School of Biomedical Sciences, King's College London, Hodgkin Building, Guy's Campus, SE1 1UL, London, UK.


This review focuses on nicotinic--serotonergic interactions in the central nervous system (CNS). Nicotine increases 5-hydroxytryptamine (5-HT) release in the cortex, striatum, hippocampus, dorsal raphé nucleus (DRN), hypothalamus, and spinal cord. As yet, there is little firm evidence for nicotinic receptors on serotonergic terminals and thus nicotine's effects on 5-HT may not necessarily be directly mediated, but there is strong evidence that the 5-HT tone plays a permissive role in nicotine's effects. The effects in the cortex, hippocampus, and DRN involve stimulation of 5-HT(1A) receptors, and in the striatum, 5-HT(3) receptors. The 5-HT(1A) receptors in the DRN play a role in mediating the anxiolytic effects of nicotine and the 5-HT(1A) receptors in the dorsal hippocampus and lateral septum mediate its anxiogenic effects. The increased startle and anxiety during nicotine withdrawal is mediated by 5-HT(1A) and 5-HT(3) receptors. The locomotor stimulant effect of acute nicotine is mediated by 5-HT(1A) receptors and 5-HT(2) receptors may play a role in the expression of a sensitised response after chronic nicotine treatment. Unfortunately, the role of 5-HT(1A) receptors in mediating nicotine seeking has not yet been investigated and would seem an important area for future research. There is also evidence for nicotinic--serotonergic interactions in the acquisition of the water maze, passive avoidance, and impulsivity in the five-choice serial reaction task.

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